How to beat childhood cancer

The drugs being used to treat children with cancer were discovered in the 1950s and 1960s, and what is needed now
is the development of more effective, less toxic therapies

By Peter Adamson

As a result of these advances in science and supportive care, the same chemotherapeutic drugs could be delivered much more intensively for children with select types and sub-types of cancer.

With selective intensification, cure rates began to increase steadily.

However, while this strategy has resulted in better outcomes, the acute and long-term morbidity of therapy has been substantial. Children with high-risk cancers who receive dose-intensive chemotherapy have a greater than 80 percent chance of experiencing at least one severe, life-threatening or fatal drug-related toxic event over the course of their treatment.

The late effects of cancer treatment include permanent organ and tissue damage, hormonal and reproductive dysfunction and second cancers.

More than 40 percent of the estimated 330,000 survivors of childhood cancer in the US experience a significant health-related complication from childhood cancer and its treatment. Despite our advances, cancer in developed countries remains the leading cause of death from disease in children older than one year.

We are, however, entering an era of unprecedented discovery. The powerful research tools that are now available to uncover the underlying basis of childhood cancers could fundamentally change how we treat children with these dreaded diseases. For a limited number of childhood cancers, there are new drugs that can target the fundamental drivers of malignancy. The most notable example is the impact of Gleevec (imatinib mesylate) on outcomes for children with an uncommon subtype of leukemia — Philadelphia chromosome-positive ALL.

The addition of this inhibitor to intensive chemotherapy has dramatically improved the outlook for these children, increasing the rate of three-year event-free survival from 35 percent to 80 percent. The development of targeted new agents is likely to affect outcomes for other subtypes of childhood cancer, including anaplastic large-cell lymphoma and other types of leukemias.

Given that childhood cancers are all rare or ultra-rare diseases, the ability of the biopharmaceutical industry to invest resources into development of new treatments is limited at best. Yet research is needed to identify potential targets for the entire spectrum of childhood cancers. For some potential targets, public-private partnerships will be needed to develop new therapeutic approaches.

The past 40 years have demonstrated the remarkable return on investment to be gained in collaborative scientific research. Now we must leverage current scientific opportunities and invest the resources needed to develop more effective, less toxic therapies, thereby improving outcomes for all children with cancer.

Peter Adamson is chair of the Children’s Oncology Group at the Children’s Hospital of Philadelphia.